4-95318381-G-A

Variant names:

• chr4-95318381-G-A
• rs13116085
• NM_003728.4:c.347-16632C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003728.4(UNC5C):​c.347-16632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,976 control chromosomes in the GnomAD database, including 16,252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (16252 hom., cov: 31)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 1 publications found

Genes affected

UNC5C (HGNC:12569): (unc-5 netrin receptor C) This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	NM_003728.4	MANE Select	c.347-16632C>T		intron	N/A	NP_003719.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	ENST00000453304.6	TSL:1 MANE Select	c.347-16632C>T		intron	N/A	ENSP00000406022.1
	UNC5C	ENST00000513796.5	TSL:1	c.347-16632C>T		intron	N/A	ENSP00000426924.1
	UNC5C	ENST00000506749.5	TSL:1	c.347-16632C>T		intron	N/A	ENSP00000426153.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65479 AN: 151858 Hom.: 16243 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65506 AN: 151976 Hom.: 16252 Cov.: 31 AF XY: 0.435 AC XY: 32279 AN XY: 74272

African (AFR) AF: 0.181 AC: 7528 AN: 41484

American (AMR) AF: 0.534 AC: 8152 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4250 AN: 5132

South Asian (SAS) AF: 0.582 AC: 2797 AN: 4806

European-Finnish (FIN) AF: 0.461 AC: 4864 AN: 10550

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.508 AC: 34496 AN: 67948

Other (OTH) AF: 0.465 AC: 982 AN: 2110

Alfa AF: 0.339 Hom.: 1096

Bravo AF: 0.425

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.76
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13116085; hg19: chr4-96239532;